Stabilisation of polypeptides
A method for preserving a polypeptide comprising: (a) providing an aqueous solution of (i) the polypeptide, (ii) one or more sugars, and (iii) a compound of formula (I) or a physiologically acceptable salt or ester thereof and/or a compound of formula (II) or a physiologically acceptable salt or ester thereof; and (b) drying the solution to form a composition incorporating the polypeptide.
1. A method for preserving a polypeptide during freeze-drying comprising:
(a) providing a buffered aqueous solution comprising:
(i) the polypeptide, and
(ii) as the sole excipients:
one or more sugars,
a compound of formula (IA) or a physiologically acceptable salt or ester thereof,
and
optionally a compound of formula (II) or a physiologically acceptable salt or ester thereof,
wherein:
R 1 represents hydrogen;
R 2 represents C 1-4 alkyl;
R 3 represents C 1-4 alkyl; and
R 4 represents hydrogen;
wherein:
X represents —S(O) 2 —;
R a and R b independently represent C 1-4 alkyl; and
(b) freeze-drying the solution to form a composition incorporating the polypeptide,
wherein the polypeptide is an antibody or antigen-binding fragment of an antibody, and wherein the buffered aqueous solution does not comprise an aluminium salt adjuvant.
2. The method according to claim 1 wherein the aqueous solution comprises a compound of formula (I) or a physiologically acceptable salt or ester thereof and a compound of formula (II) or a physiologically acceptable salt or ester thereof.
3. The method according to claim 1 , wherein the compound of formula IA is dimethylglycine or a physiologically acceptable salt or ester thereof.
4. The method according to claim 1 , wherein (a) the concentration of the compound of formula IA or a physiologically acceptable salt or ester thereof is from 0.001M to 2.5M, and/or (b) the concentration of the optional compound of formula (II) or a physiologically acceptable salt or ester thereof is from 0.001 M to 2.5M, and/or (c) the sugar concentration, or total sugar concentration, is from 0.05M to 3M.
5. The method according to claim 1 , wherein (a) the one or more sugars comprise a non-reducing sugar or sugar alcohol, and/or (b) two or more sugars are used and one of the sugars is sucrose, and/or (c) two or more sugars are used, one of the sugars is sucrose and the ratio of the concentration of sucrose relative to the other sugar(s) is from 1:1 to 20:1.
6. The method according to claim 5 wherein the other sugar is raffinose.
7. The method according to claim 1 , wherein one sugar is present which is mannitol.
8. The method according to claim 1 in which the aqueous solution is freeze-dried in vials or ampoules which are then optionally sealed.
9. The method according to claim 1 , wherein the polypeptide is (i) a monoclonal antibody or a fragment of a monoclonal antibody, or (ii) a chimeric, humanized or human antibody, or a fragment of a chimeric, humanized or human antibody.
10. The method according to claim 1 , wherein the compound of formula (II) is dimethylsulfone.
11. The method according to claim 3 , wherein the compound of formula (II) is dimethylsulfone.